The principal aim of this project is to test the hypothesis of general multispecificity for antibody combining regions and other types of receptors. Receptor sites should be capable of binding an occasional disparately structured ligand with an association constant large enough potentially to affect biological function. Radiolabeled antibodies or receptor-bearing molecules will be screened for multispecific binding to many, large haptens each bound to a separate affinity column matrix. Large haptenic reagents have been synthesized for this purpose using methods of peptide synthesis. Monoclonal antibodies from myelomas and hybridomas are being studied first. Multispecific bindings will be studied further by quantitative affinity chromatography. Collaborative studies bearing on issues of specificity in immune responses have been and are being carried out; they deal with molecular interpretations of cellular mechanisms in immune responses. Chemical methods such as heteroligation and use of heterobifunctional reagents are employed in preparing specially designed antigenic materials, test reagents, and polyfunctional probes.